Widespread and controllable distribution of viral vectors is essential to achieve human gene therapy for Parkinson's disease. Given the volume of the human striatum methods development is required for adequate vector coverage. Convection-enhanced delivery (CED), a recently developed approach for delivery of small and large molecules to targeted sites in solid tissues, utilizes a bulk flow mechanism to deliver and distribute macromolecules to clinically significant volumes of tissue. The technique is based on a pressure infusion system that "pushes" and replaces extracellular fluid in surrounding cells of the parenchyma. Delivery of fluid carrying the AAV-2 particles results in significant spread of the vector within CNS. This delivery system offers significant advantages by improving the volume of distribution, providing uniform distribution of drug concentration within the targeted tissue, and complete delivery of the therapeutic factor to the target site. AAV-2 binds to heparin-sulfate proteoglycans on the cell surface and enhances the interaction of AAV-2 with cells. As for other heparin-binding proteins the binding affinity of AAV-2 to heparin is low and a high-affinity receptor is required for cell transduction. Preliminary data indicate that heparin addition to AAV-2 particles allows for robust convection based delivery of AAV-2 within anatomical structures. This project will systematically examine the impact of combined CED along with heparin to distribute AAV throughout the monkey striatum. The same methodologies will be tested will also be applied to VSV-g pseudotyped lentivirus vectors.